Alkylphospholipids (APL) are promising anticancer drugs. We have found that interaction of APL liposomes with cells depends on membrane domain structure, defined by liposome cholesterol content. Liposomes with less than 50 mol% cholesterol fuse with cells, while those with more cholesterol, where the proportion of disordered domains decreases below 10%, don’t. We proposed that fluid domains are responsible for fusion. Results suggest that micelles are not the only reason for cytotoxic effect of APL formulation, but liposomes with less than 50 % cholesterol also contribute to cytotoxicity.
The overcome of endothelial barrier is a serious challenge in the treatment of brain tumors. Possible solution is delivery of drugs in liposome carriers of adequate composition. For this purpose liposomes of different composition were prepared and influence of membrane fluidity on the uptake and transcytosis by endothelial (MDCK) cells, a model for blood brain barrier, investigated. The most pronounced transcytosis was obtained for liposomes composed of DPPC, cholesterol, DOPC and 20 mol% alkylphospholipid that experienced the highest membrane fluidity among the liposomes investigated.
For many investigations on cells and interactions of biologically active substances with cells detachment from the bottom of the culture dishes is necessary. However, detachment can cause severe damage to cells and influence the reliability of the results. According to our results, among the detachment procedures used (scraping cells, removal by citrate buffer or trypsin) the most suitable seems to be trypsinistation, which influences cell viability and metabolism of cells the least, while neither of the methods influence membrane fluidity significantly.
In many liposome formulations lipids forms not only unilamellar or multilamellar vesicles but also micelles. Amount of micelles depends strongly on liposome composition. We have developed the procedure by which it is possible to determine the amount of micelles in liposome formulation by EPR. We have applied the procedure to OPP liposomes with different amount of cholesterol. For liposome formulation of OPP this is of special importance since they can be potentially used in cancer therapy, but in micellar form they produce serious side effects, like hemolysis.